The pH Effects on SARS-CoV and SARS-CoV-2 Spike Proteins in the Process of Binding to hACE2

Abstract

COVID-19 has been threatening human health since the late 2019, and has a significant impact on human health and economy. Understanding SARS-CoV-2 and other coronaviruses is important to develop effective treatments for COVID-19 and other coronavirus-caused diseases. In this work, we applied multi-scale computational approaches to study the electrostatic features of spike (S) proteins for SARS-CoV and SARS-CoV-2. From our results, we found that SARS-CoV and SARS-CoV-2 have similar charge distributions and electrostatic features when binding with the human angiotensin-converting enzyme 2 (hACE2). Energy pH-dependence calculations revealed that the complex structures of hACE2 and the S proteins of SARS-CoV/SARS-CoV-2 are stable at pH values ranging from 7.5 to 9. Three independent 100 ns molecular dynamics (MD) simulations were performed using NAMD to investigate the hydrogen bonds between S proteins RBD and hACE2 RBD. From MD simulations, we found that SARS-CoV-2 forms 19 pairs (average of three simulations) of hydrogen bonds with high occupancy (>50%) to hACE2, compared to 16 pairs between SARS-CoV and hACE2. Additionally, SARS-CoV viruses prefer sticking to the same hydrogen bond pairs, while SARS-CoV-2 tends to have a larger range of selections on hydrogen bonds acceptors. We also labelled key residues involved in forming the top five hydrogen bonds that were found in all three independent 100 ns simulations. This identification is important to potential drug designs for COVID-19 treatments. Our work will shed the light on current and future coronavirus-caused diseases.

Evolutionary progression of collective mutations in Omicron sub-lineages towards efficient RBD-hACE2: Allosteric communications between and within viral and human proteins

“…Residues at positions 339, 452, 478, 493 and 498 changed from a non-polar/uncharged residue in the WT to a polar/positively charged residue in the Omicron sub-lineage. The hACE2 interface is predominately negatively charged [98] ; consequently, a more positively charged RBD interface would suggest increased RBD-hACE2 electrostatic interaction.…”

Electrostatic features for the Receptor binding domain of SARS-COV-2 wildtype and its variants. Compass to the severity of the future variants with the charge-rule

“…refs. [23][24][25][26][27][28][29][30][31][32][33][34][35][36] ). Most of the studies have focused on the interactions involving the receptor-binding domain (RBD) of the SARS-CoV-2 spike homotrimer glycoprotein due to its biological central relevance.…”

Monoclonal antibodies: a remedial approach to prevent SARS-CoV-2 infection

“…Drugs that can treat serious medical conditions and illnesses that arises due to SARS-CoV-2 are still urgently needed (Wang et al 2021 ). Recently, according to the computational approach, the complex of hACE2 and S-protein of both SARS-CoV-2 and SARS-CoV were found to be most stable at pH 7.5–9 (Sharma and Deep 2020 ; Xie et al 2022 ). Moreover, the patients having Burkitt’s oesophagus and patients under a proton pump inhibitor regimen are more vulnerable to increased severity of infection due to higher expression of ACE2 receptor augmenting SARS-CoV-2 entry (Jimenez et al 2021 ).…”